Benzyl N-[(Benzyloxy)methyl]carbamate: An Improved Aminomethylation Electrophile for the Synthesis of (Benzyloxy)carbonyl (Cbz)-Protected Chiral β2-Amino Acids

α-Aminomethylation of (R)-DIOZ-alkylated (DIOZ=4-isopropyl-5,5-diphenyloxazolidin-2-one) substrates is a key step in the asymmetric synthesis of β2-amino acids, but it is unfortunately often accompanied by formation of transcarbamation by-products. Aminomethylation was tested using a range of electrophiles, and the amount of by-product formation was assessed in each case. Benzyl N-[(benzyloxy)methyl]carbamate electrophile 3d is unable to form this by-product due to its inherent benzyl substitution. Use of electrophile 3d showed an improved impurity profile in aminomethylation, thus leading to easier intermediate purification.